Summary Obsessive-compulsive disorder has been studied from several different perspectives since the beginning of this project in 1980. During the past year, the major focus has been to test the hypothesis that serotonergic function might be alterd in patients with this disorder. This hypothesis, which was generated from several promising clinical trials with the tricyclic antidepressant clomipramine, was examined by (1) measuring the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (2) assaying serotonin uptake and [3H]-imipramine binding in platelets, and (3) comparing neuroendocrine response to the serotonergic agent fenfluramine in obsessional patients and matched controls. On each of these measures, the patients were not significantly different from controls. Furthermore, in a double blind treatment comparison of the serotonin uptake inhibitor zimelidine and the noradrenergic uptake inhibitor desipramine, neither drug was found to be as effective as clomipramine. These findings suggest that serotonin uptake, turnover. and receptor sensitivity are not altered in obsessional patients, and that pharmacologic blockade of serotonin uptake is not sufficient for the reduction of obsessional symptoms.